The subject of the present invention is a device for measuring the pH of an appropriate target, particularly a tumour, a method for using said device as well as its applications, particularly to the control of treatment of tumours by hyperthermy.
The early detection of tumours is essential for improving their prognosis; however, tumours of organs or of tissues are often difficult to detect and, in the case of cancer of the oesophagus, for example, the advent of oesophageal fibroscopy has not resulted in it being diagnosed at an earlier stage.
Other methods of early diagnosis have been proposed and involve a number of techniques:
1--fixation of a contrast agent or of a colouring agent and diagnosis by imaging; the colouring agent can either have a great affinity for nucleic acids (toluidine blue, for example) or, on the contrary, not have tumorous fixation (Lugol's solution, for example, which only reacts with glycogen of differentiated malpighian epithelium) or finally by the use of photosensitisers having a fluorescence peak during suitable light excitation (photodiagnosis). These techniques involve producing a fluorescence gradient between healthy tissue and tumorous tissue, which requires the elective fixation or the specific retention of the marker by the tumour; thus, these depend on many factors and especially on the vascularisation, the necrosis and the phagocytic capacity of the tumour.
2--the use of monoclonal antibodies or the vectorisation of the marker by liposomes; this technique, used on its own, has the disadvantage of requiring specific and expensive reagents.
3--the spectral study of the emitted fluorescence. This last method, which does not require the use of specific reagents, can avoid the abovementioned disadvantages.
It is possible to mention, as diagnostic methods using the spectral study of the emitted fluorescence:
the diagnostic method proposed by S. Andersson-Engels et al. (Lasers in Medical Science, 1988, 4, 171-181), which describes the localisation and detection of atheroma patches by measuring the self-fluorescence induced by a laser as the source of light excitation;
diagnosis of tumours by analysis of the fluorescence, which has especially been described in:
the article in the name of R. R. Alfano et al., which appeared in J. Quantum Electronics, 1984, Vol. OE-20, 12, 1507-1511, which describes measuring the self-fluorescence induced by a laser source, both on cancerous tissues and on healthy tissues, and which shows that the spectral profiles of cancerous tissues are different from those of healthy tissues.
and the methods by induced fluorescence, as specified in the article in the name of A. E. Profio et al., which appeared in Med. Phys., 1984, 11, 4, 516-520, which describes a fluorometer for the endoscopic diagnosis of tumours. More precisely, a fluorescent derivative of hematoporphyrin is injected and the tumour is then characterised by detecting the emitted fluorescence; the source of excitation is a purple light, conveyed through an optical fibre to the endoscope, whereas the emitted fluorescence as well as the reflected purple light are collected by another optical fibre. The fluorescence in red light and in purple light are separated using a dichroic mirror and a filter, and detected using photomultipliers. This method has the disadvantage that small tumours are difficult to localise, that it is entirely dependent on the measuring conditions, and that the concentration gradient between healthy and tumorous tissues is low with, moreover, a risk of cutaneous phototoxicity.
The methods for the diagnosis of tumours, by fluorescence, proposed in the prior art have, moreover, the major disadvantage of being absolute techniques, which result in many false positives or false negatives, because they are dependent on the measuring conditions (position of the collecting fibres, for example, or structure of the tissue to be studied).
A certain number of documents describe optrodes (optic electrodes) for measuring pH (Medical & Biological Engineering & Computing, 1987, 25, 5, 597-604; IEEE Transactions on Biomedical Engineering, 1986, BME-33, 117-132); however, such optrodes have the major disadvantage of not being able to be used in an imaging system, in so far as they only make possible limited measuring, at the point of contact with the tissue concerned.